Laboratory for Marine Biology and Biotechnology of Qingdao National Laboratory for Marine Science and Technology and College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People's Republic of China.
Open Biol. 2018 Oct 31;8(10):180051. doi: 10.1098/rsob.180051.
The dysregulation of microRNAs (miRNAs), key posttranscriptional regulators of gene expression, is closely associated with cancer development. However, the miRNAs of monocytes, important cells of tumour immunity, have not been extensively explored. In the present study, the differentially expressed miRNAs of blood monocytes derived from gastric and breast cancer patients and healthy donors were characterized. The results indicated that 74 miRNAs were upregulated and 46 miRNAs were downregulated in monocytes of patients with breast or gastric cancers compared with the healthy donors, suggesting that these 120 miRNAs from transformed monocytes were associated with cancers. The differentially expressed miRNAs, 38 of which were novel, were further validated using quantitative real-time PCR. As an example, the results showed that miR-150-5p downregulated the CCR2 expression in monocytes by targeting Notch 3, thus leading to the suppression of tumorigenesis. The target gene analysis showed that 36 of the 120 miRNAs targeted cancer-related genes. KEGG pathway analysis indicated that the cancer-associated miRNAs were involved in pathways related to cancers, such as the HIF-1 signalling and the mTOR signalling pathways. Thus, our study provided new clues to comprehensively understand the relationship between miRNAs and cancers.
microRNAs(miRNAs)是基因表达的关键转录后调控因子,其失调与癌症的发生密切相关。然而,肿瘤免疫中重要的细胞——单核细胞中的miRNAs 尚未得到广泛研究。在本研究中,我们对来自胃癌和乳腺癌患者及健康供体的血液单核细胞中的差异表达 miRNA 进行了鉴定。结果表明,与健康供体相比,乳腺癌或胃癌患者的单核细胞中 74 个 miRNA 上调,46 个 miRNA 下调,提示这些来自转化单核细胞的 120 个 miRNA 与癌症有关。进一步使用定量 real-time PCR 对 38 个差异表达的 miRNA(其中 38 个是新的)进行了验证。例如,结果表明 miR-150-5p 通过靶向 Notch3 下调单核细胞中的 CCR2 表达,从而抑制肿瘤发生。靶基因分析表明,这 120 个 miRNA 中的 36 个靶向与癌症相关的基因。KEGG 通路分析表明,与癌症相关的 miRNAs 参与了与癌症相关的途径,如 HIF-1 信号通路和 mTOR 信号通路。因此,我们的研究为全面了解 miRNAs 与癌症之间的关系提供了新的线索。